Mycobacterium Tuberculosis Acquisition in Early Childhood in Uganda

Tuberculosis (TB) is the leading cause of death for people infected with HIV worldwide. Active TB disease is largely driven by a vast reservoir of latent TB infection (LTBI), most of which has already been established by the age of five. 1,2 However, the epidemiology of TB acquisition prior to the age of 5 is poorly understood in high TB burden countries. Additionally, there is a significant gap in knowledge of TB acquisition dynamics in HIV-exposed, un-infected children - a growing group of children due to advances in Prevention of Mother to Child Transmission. To characterize TB acquisition and to assess the influence of HIV-exposure on LTBI in a birth cohort of HIV-exposed and un-exposed children under the age of 5 in Tororo, Uganda, we propose a cross-sectional study of childbearing women (N=300) and their children (N=600). We will test the hypotheses that (1) there is a significant increase in prevalence of LTBI across the 0-5 year age strata and (2) HIV-exposed, un-infected children have a higher prevalence of LTBI relative to HIV-unexposed children. We will also investigate the influence of nutritional status, socioeconomic status, and maternal LTBI on the childhood LTBI and interactions with HIV exposure. To measure LTBI we will use the tuberculin skin test and the Interferon Gamma Release Assay, and analyze concordance between the two tests. Subject enrollment and LTBI measurement will take place over 10 months and the analysis will occur over 3 months. This study will leverage the existing research infrastructure of the NIH-funded MU-UCSF collaboration that maintains well-characterized cohorts of childbearing women and children. The results of this research will provide preliminary data for an NIH mentored K23 award to further describe the epidemiology of early TB acquisition and design household-based prevention interventions to reduce the latent TB reservoir in East Africa.